As semiconductor devices continue to be manufactured on smaller scales, inspection systems are required to detect and analyze sample defects of interest (DOI) with increased accuracy and precision. Often a sample, such as a wafer or a reticle, is imaged multiple times to generate more data, which can be processed (i.e. combined and/or compared) to filter out nuisance and isolate data associated with DOI. When the sample is imaged multiple times, possibly using different illumination wavelength and/or aperture settings, throughput is reduced. Moreover, machine drifts or vibrations can offset the inspected location on the sample from run to run and complicate alignment of the sample images due to lack of clear and/or similar features. This alignment uncertainty, as well as temporal fluctuations in the imaging system, increases inspection noise and reduces the benefits of multi-wavelength inspection.